Publications by authors named "Thoms J"
Study Objectives: Cancer-related fatigue is one of the most common symptoms in cancer survivors. Cognitive behavioural therapy for insomnia (CBT-I) can improve fatigue, but mechanisms are unclear. This secondary analysis of a randomized controlled trial evaluated whether CBT-I led to a significant improvement in fatigue, accounting for change in comorbid symptoms of insomnia, perceived cognitive impairment (PCI), anxiety, and depression.
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- Hypomethylating agents (HMAs) are key treatments for Myelodysplastic Neoplasms (MDS) and Acute Myeloid Leukemia (AML), but patients often develop resistance and experience treatment failure.
- Researchers conducted a genome-wide CRISPR-Cas9 screen in MDS-derived cells, discovering that targeting the gene TOPORS enhances the effectiveness of HMAs by making cancer cells more vulnerable to DNA damage.
- The study suggests that combining HMAs with strategies to inhibit SUMOylation or TOPORS could be an effective treatment approach for patients with high-risk MDS or AML, without harming normal blood cell production.
Purpose: Comorbid insomnia and cancer-related cognitive impairment (CRCI) are experienced by up to 26% of individuals diagnosed with cancer. This study examined the efficacy and durability of cognitive behavioral therapy for insomnia (CBT-I) on perceived CRCI in cancer survivors.
Methods: Atlantic Canadian cancer survivors with insomnia and CRCI were randomly assigned to receive seven weekly virtual CBT-I sessions (n = 63) or placed in a waitlist control group (n = 69) to receive treatment after the waiting period.
Aging is associated with the steady decline of several cellular processes. The loss of skeletal muscle mass, termed sarcopenia, is one of the major hallmarks of aging. Aged skeletal muscle exhibits a robust reduction in its regenerative capacity due to dysfunction (i.
View Article and Find Full Text PDFPenile cancer is a rare genitourinary malignancy for which limited treatment options exist beyond primary surgical resection. Metastatic lymphadenopathy represents a particularly poor prognosis with a lack of literature to suggest the effectiveness of radiation or systemic therapies. Our case documents an inguinal recurrence of penile squamous cell carcinoma not amenable to surgical intervention demonstrating complete response to salvage radiotherapy in the palliative setting.
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- The BloodChIP Xtra database offers extensive resources for studying transcription factor occupancy and chromatin structure in human hematopoietic stem and progenitor cells, as well as acute myeloid leukemia (AML) cell lines.
- Compared to its predecessor, BloodChIP, this new database contains more datasets, utilizing improved techniques for analyzing rare cell types in both healthy and AML contexts.
- It is designed for user-friendly access, allowing users to easily query data, export findings for gene networks, and analyze gene associations with specific cellular processes.
Article Synopsis
- The ERG transcription factor is linked to various cancers, particularly leukemia, but its specific mechanisms and interactions are not well understood.
- Our research highlights the importance of proline at position 199 in the PNT domain of ERG, which is essential for its role in promoting leukemia by enabling self-renewal and inhibiting myeloid differentiation.
- We found that proline 199 allows ERG to interact with the NCoR-HDAC3 co-repressor complex, and blocking HDAC3 slows down the growth of cancers driven by ERG, suggesting that targeting this interaction could be a new treatment strategy.
Article Synopsis
- Hematopoietic stem and progenitor cells (HSPCs) require a specific combination of seven transcription factors (TFs) to manage their differentiation into various blood cell types, but their precise roles are still unclear.
- The study used advanced techniques to analyze chromatin interactions and TF binding in different HSPC subtypes, revealing that TF activity and enhancer-promoter interactions differ significantly among these cell types, which correlates with how genes are expressed.
- Findings indicate that certain TF combinations are linked to specific blood cell lineages, and these combinations may also prime regulatory regions for future binding by lineage-specific TFs, providing insights into both normal blood cell formation and potential disruption in leukemia.
Article Synopsis
- Myelodysplastic neoplasms (MDS) and chronic myelomonocytic leukemia (CMML) are diseases caused by mutations in blood stem cells that affect blood production.
- Hypomethylating agents (HMAs) can help manage these conditions without needing to eliminate all mutated cells, possibly improving the function of the remaining stem cells.
- The study analyzed the mutations in different blood cell types before and after treatment to understand how these mutated stem cells behave and contribute to better blood counts following HMA therapy.
Article Synopsis
- Hypomethylating agents are used in cancer treatment, but their potential to reactivate oncogenes remains unclear.
- In a study of myelodysplastic syndrome patients, 40% and 30% showed up-regulation of a specific oncogene after treatment, which correlated with worse outcomes.
- CRISPR-DiR technology identified a critical CpG island for oncogene expression; this highlights the need for further research into the effects of hypomethylating agents on cancer treatment.
Article Synopsis
- Oncofetal protein SALL4 is important for the survival of cancer cells, but targeting it only works for patients with SALL4-positive tumors.
- Researchers discovered that by artificially introducing SALL4 in SALL4-negative cancer cells, these cells became partially reliant on SALL4 for survival, which could be exploited for treatment.
- Using the FDA-approved drug 5-aza-2'-deoxycytidine (DAC) to induce SALL4 expression in these cancer cells made them more sensitive to another drug, entinostat, allowing for a new therapeutic strategy for previously untreatable patients.
Article Synopsis
- Men with prostate cancer who are treated with testosterone-blocking therapy (ADT) may have trouble with thinking and remembering things.
- The study looked at 83 men on ADT and compared them to other groups to see how insomnia (trouble sleeping) impacted their thinking.
- Results showed that sleep problems made it harder for these men to feel good about their thinking skills, especially if they were feeling really tired or sad.
Objectives: This paper (1) sought to compare sleep, mood and physical symptom profiles of men with prostate cancer (PCa) who experienced subjective and objective cancer-related cognitive impairment (CRCI) during the first year of treatment and (2) examine if fluctuations in mood and physical symptoms are associated with change in subjective or objective CRCI.
Methods: This prospective observational cohort study examined 24 new patients with PCa receiving androgen deprivation therapy (ADT) and radiation therapy (RT) during the first 12 months of treatment. Participants completed subjective and objective assessments of cognition, sleep continuity and self-report measures of insomnia, fatigue, depression and anxiety.
Article Synopsis
- Changes in gene regulation are crucial for hematopoietic stem cells to transition into different blood cell types, but this process gets disrupted in leukemia.
- Researchers hypothesized that understanding the core gene regulatory networks in healthy and leukemic cells could shed light on these disruptions.
- A group of seven transcription factors showed a strong, interconnected circuit in both healthy and leukemic cells that could be targeted to encourage proper cell transitions and potentially improve treatments for leukemia.
Perceived cognitive impairment (PCI) and sleep disturbances (such as insomnia) are commonly reported barriers preventing cancer survivors from resuming normal functioning. Cognitive-behaviour therapy for insomnia (CBT-I) is the treatment of choice for insomnia among cancer survivors. Literature suggests that treatment with CBT-I may lead to an improvement in PCI, but this needs to be tested in a sample of patients with PCI at study entry with cognitive impairments as the primary study outcome.
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- Terminally differentiated mouse osteocytes and adipocytes can be transformed into multipotent stem cells using specific growth factors and chemicals.
- The research has refined methods for reprogramming human adipocytes into induced multipotent stem (iMS) cells and highlighted their unique molecular traits.
- In various injury models, these iMS cells successfully contributed to the regeneration of muscle, bone, and other tissues without causing abnormal tissue growth or tumors.
Article Synopsis
- Overexpression of SNAI1, a key regulator of the epithelial-to-mesenchymal transition (EMT), is shown to play a significant role in the development of human acute myeloid leukemia (AML) by affecting cell differentiation and promoting the growth of immature myeloid cells.
- Research indicates that elevated SNAI1 levels can lead to increased self-renewal and proliferation of these cells, suggesting its importance in AML pathology.
- The study highlights a previously unknown interaction between SNAI1 and the histone demethylase KDM1A/LSD1, providing new insights into leukemia mechanisms and potential treatment strategies involving LSD1 inhibitors.
The ability to produce second-generation itaconic acid by Aspergillus terreus, and the inhibitory effects of hydrolysis by-products on the fermentation were evaluated by cultivation in a synthetic medium containing components usually present in a real hydrolysate broth from lignocellulosic biomasses. The results showed that A. terreus NRRL 1960 can produce itaconic acid and consume xylose completely, but the conversion is less than the fermentation using only glucose.
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- High-CHK1 activity is prevalent in glioblastoma (GBM) and may influence tumor development and patient survival, but its exact role is unclear.
- Research shows that the levels of CHK1 and the oncogene CIP2A are independent indicators of poorer survival rates in glioma patients.
- CHK1 and pSTAT3 work together to regulate CIP2A expression, and disrupting this pathway could slow down GBM growth, suggesting CIP2A as a potential target for new cancer therapies.
Telomerase is a ribonucleoprotein complex that maintains the length and integrity of telomeres, and thereby enables cellular proliferation. Understanding the regulation of telomerase in hematopoietic cells is relevant to the pathogenesis of leukemia, in which telomerase is constitutively activated, as well as bone marrow failure syndromes that feature telomerase insufficiency. Past studies showing high levels of telomerase in human erythroblasts and a prevalence of anemia in disorders of telomerase insufficiency provide the rationale for investigating telomerase regulation in erythroid cells.
View Article and Find Full Text PDFIntroduction: Studies that use objective assessments often only recruit individuals in the geographic region in which the study is being conducted, because the assessments require that the researcher and participant be face to face. This limits the number and variety of individuals who can participate. Telehealth is one approach that could be used to increase sample size and representativeness.
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- * Researchers are using genome-wide techniques to better understand how AML affects hematopoietic stem cell transcriptional networks, revealing mechanisms that allow AML cells to avoid differentiation and maintain self-renewal.
- * The goal is to leverage this understanding to find critical points within these disrupted networks that can be targeted by new therapies aimed at treating AML more effectively.
Article Synopsis
- Identification of HMGA2 is crucial for understanding hematopoietic stem cell (HSC) behavior and improving their clinical applications in treating blood-related disorders.
- High levels of HMGA2 are found in HSCs and immature progenitors, and reducing its expression diminishes the long-term repopulation ability of cord blood-derived stem cells.
- Enhancing HMGA2 expression in these cells boosts their reconstitution capabilities and favors development into specific blood lineages, indicating its significant role in regulating both cell growth and differentiation.